title: A molecular basis for NKT cell recognition of CD1d-self-antigen.
abstract: The antigen receptor for natural killer T cells (NKT TCR) binds CD1d-restricted microbial and self-lipid antigens, although the molecular basis of self-CD1d recognition is unclear. Here, we have characterized NKT TCR recognition of CD1d molecules loaded with natural self-antigens (Ags) and report the 2.3 Å resolution structure of an autoreactive NKT TCR-phosphatidylinositol-CD1d complex. NKT TCR recognition of self- and foreign antigens was underpinned by a similar mode of germline-encoded recognition of CD1d. However, NKT TCR autoreactivity is mediated by unique sequences within the non-germline-encoded CDR3β loop encoding for a hydrophobic motif that promotes self-association with CD1d. Accordingly, NKT cell autoreactivity may arise from the inherent affinity of the interaction between CD1d and the NKT TCR, resulting in the recognition of a broad range of CD1d-restricted self-antigens. This demonstrates that multiple self-antigens can be recognized in a similar manner by autoreactive NKT TCRs.
authors.affiliation: Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Thierry
authors.initials: T
authors.lastname: Mallevaey
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Clarke
authors.forename: James P
authors.initials: JP
authors.lastname: Scott-Browne
authors.forename: Mary H
authors.initials: MH
authors.lastname: Young
authors.forename: Laila C
authors.initials: LC
authors.lastname: Roisman
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pellicci
authors.forename: Onisha
authors.initials: O
authors.lastname: Patel
authors.forename: Julian P
authors.initials: JP
authors.lastname: Vivian
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Matsuda
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Laurent
authors.initials: L
authors.lastname: Gapin
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology*; D001324:Autoantigens; D018360:Crystallography, X-Ray; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D046912:Multiprotein Complexes; D055611:Natural Killer T-Cells / Q000276:immunology*; D055607:Receptors, Natural Killer Cell / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; D001324:Autoantigens; D046912:Multiprotein Complexes; D055607:Receptors, Natural Killer Cell